Department of Medical Laboratory Science, College of Medicine and Health Sciences, Aksum University, Aksum, Ethiopia.
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
Sci Rep. 2023 Apr 21;13(1):6546. doi: 10.1038/s41598-023-33850-4.
With the widespread use of Integrase strand transfer inhibitors (INSTIs), surveillance of HIV-1 pretreatment drug resistance is critical in optimizing antiretroviral treatment efficacy. However, despite the introduction of these drugs, data concerning their resistance mutations (RMs) is still limited in Ethiopia. Thus, this study aimed to assess INSTI RMs and polymorphisms at the gene locus coding for Integrase (IN) among viral isolates from ART-naive HIV-1 infected Ethiopian population. This was a cross-sectional study involving isolation of HIV-1 from plasma of 49 newly diagnosed drug-naive HIV-1 infected individuals in Addis-Ababa during the period between June to December 2018. The IN region covering the first 263 codons of blood samples was amplified and sequenced using an in-house assay. INSTIs RMs were examined using calibrated population resistance tool version 8.0 from Stanford HIV drug resistance database while both REGA version 3 online HIV-1 subtyping tool and the jumping profile Hidden Markov Model from GOBICS were used to examine HIV-1 genetic diversity. Among the 49 study participants, 1 (1/49; 2%) harbored a major INSTIs RM (R263K). In addition, blood specimens from 14 (14/49; 28.5%) patients had accessory mutations. Among these, the M50I accessory mutation was observed in a highest frequency (13/49; 28.3%) followed by L74I (1/49; 2%), S119R (1/49; 2%), and S230N (1/49; 2%). Concerning HIV-1 subtype distribution, all the entire study subjects were detected to harbor HIV-1C strain as per the IN gene analysis. This study showed that the level of primary HIV-1 drug resistance to INSTIs is still low in Ethiopia reflecting the cumulative natural occurrence of these mutations in the absence of selective drug pressure and supports the use of INSTIs in the country. However, continues monitoring of drug resistance should be enhanced since the virus potentially develop resistance to this drug classes as time goes by.
随着整合酶抑制剂（INSTIs）的广泛使用，在优化抗逆转录病毒治疗效果方面，对 HIV-1 治疗前耐药性进行监测至关重要。然而，尽管这些药物已经问世，但在埃塞俄比亚，有关它们的耐药突变（RMs）的数据仍然有限。因此，本研究旨在评估新诊断为未经抗逆转录病毒治疗的 HIV-1 感染的埃塞俄比亚人群中病毒分离株中整合酶（IN）基因编码区的 INSTI RMs 和多态性。这是一项横断面研究，涉及 2018 年 6 月至 12 月期间从亚的斯亚贝巴新诊断为未经药物治疗的 HIV-1 感染的 49 名个体的血浆中分离 HIV-1。使用内部检测法扩增并测序了涵盖血液样本前 263 个密码子的 IN 区。使用斯坦福 HIV 耐药性数据库中的校准人群耐药性工具版本 8.0 检查 INSTIs RMs，同时使用 REGA 版本 3 在线 HIV-1 亚型工具和 GOBICS 的跳跃轮廓隐马尔可夫模型检查 HIV-1 遗传多样性。在 49 名研究参与者中，有 1 名（1/49；2%）携带主要的 INSTIs RM（R263K）。此外，有 14 名（14/49；28.5%）患者的血液标本存在辅助突变。其中，M50I 辅助突变的频率最高（13/49；28.3%），其次是 L74I（1/49；2%）、S119R（1/49；2%）和 S230N（1/49；2%）。关于 HIV-1 亚型分布，根据 IN 基因分析，所有研究对象均被检测为携带 HIV-1C 株。本研究表明，在埃塞俄比亚，HIV-1 对 INSTIs 的原发性耐药水平仍然较低，这反映了在没有选择压力的情况下这些突变的累积自然发生，并支持在该国使用 INSTIs。然而，随着时间的推移，病毒有可能对这些药物产生耐药性，因此应加强对耐药性的持续监测。
